Summary

Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ
transplant recipients to prevent their bodies from rejecting the new organ. Long-term use of
these drugs places transplant recipients at higher risk of serious infections and certain
types of cancer. The purpose of this study is to determine whether immunosuppressive drugs
can be safely withdrawn over a minimum of 9 months from children who received liver
transplants at least 4 years ago.

Study Design

Recipients of parental living donor liver transplants 4 or more years prior to trial enrollment, who also had stable allograft function during the preceding 6 months while taking a single immunosuppressive drug were permitted to undergo withdrawal of immunosuppression therapy. With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks.
Patients are carefully evaluated/monitored throughout the study by assessments including but not limited to liver biopsy, liver tests and clinic visits, alloantibodies, autoantibodies and quantitative immunoglobulin G test results.

gradual withdrawal of immunosuppressive medication

With high dose, daily dose reduction by 25% for 8 weeks. With low dose, daily dose reduction by 25% for 4 weeks.

Primary Outcomes

Measure

Proportion of Subjects Successfully Withdrawn From Immunosuppression

time frame:
1 year after completion of immunosuppression withdrawal

Proportion of Patients Who Suffer Graft Loss or Die Following Initiation of Immunosuppression Withdrawal

time frame:
1 year

Secondary Outcomes

Measure

Time From Start of Immunosuppression to the First Episode of Acute Rejection or to Diagnosis of Chronic Rejection

time frame:
Immunosuppression to first acute rejection or diagnosis of chronic rejection

Eligibility Criteria

Male or female participants from 4 years up to 18 years old.

Inclusion Criteria for Liver Recipients:
- Received liver from living parent donor
- Received transplant at least 4 years prior to study entry
- Less than 18 years of age at time of transplant
- Parent or guardian willing to provide informed consent
Inclusion Criteria for Liver Donors:
- Willing to participate in this study
Exclusion Criteria for Liver Recipients:
- Underwent transplant because of liver failure related to autoimmune disease
- Underwent transplant of a second organ simultaneously with or after liver transplant
OR liver retransplantation
- Receiving immunosuppression with more than one drug
- 50% increase in dose of current immunosuppressive drug
- HIV infection
- Hepatitis B or C virus infection
- Pregnancy or breastfeeding

Additional Information

In order to prevent the rejection of transplanted organs, transplant recipients are
prescribed a strict, lifelong regimen of immunosuppressive drugs. While these drugs help
prevent the body from rejecting the transplant, they carry numerous complications, including
increased risk of serious infections and certain types of cancer. However, there is mounting
evidence that a significant percentage of liver transplant recipients can maintain a
healthy, functioning transplant without ongoing immunosuppression. This study will determine
whether gradual withdrawal and eventual discontinuation of all immunosuppressive medication
can be safely accomplished in children who received a liver transplant from a parent. Twenty
eligible patients who were under 18 years old at the time of transplant, whose donor was a
parent, and who received the transplant at least four years ago will be enrolled in the
study.
Liver recipients will have an initial screening assessment consisting of a medical history,
liver biopsy, and urine and blood collection. Eligible recipients will be placed on a
modified medication schedule to gradually decrease their immunosuppression medication slowly
over a 9- to 12-month period, during which time they will be closely monitored by study
staff. Immunosuppressive drugs will not be provided by this study. For a minimum of 3 and up
to a maximum of 7 years, monthly telephone consultations and quarterly study visits will
occur. Visits will include physical exams and blood collection to monitor the children's
health during the withdrawal phase. The exact schedule of immunosuppressant withdrawal will
be determined by study physicians based on participant's health and immune function test
results. Donor and nondonor parents will be asked to each provide one blood sample during
the initial study visits for immunologic and genetic testing.
*** IMPORTANT NOTICE: *** The National Institute of Allergy and Infectious Diseases and the
Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy
for recipients of cell, organ, or tissue transplants outside of physician-directed,
controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can
result in serious health consequences and should only be performed in certain rare
circumstances, upon the recommendation and with the guidance of your health care provider.